General

Physiology

Pharmacokinetic and pharmacodynamic changes

Therefore, ↓ V_D for water-soluble drugs, ↑ V_D for fat-soluble drugs.

Specific drugs

Anticholinergics. Increased V_D atropine with ↑ half-life. Causes central anticholinergic syndrome unlike glycopyrrolate because of passage across blood–brain barrier.

Barbiturates. Larger V_D with prolonged clearance; 30–40% ↓ dose requirement.

Benzodiazepines (Table 6.1). Increased CNS sensitivity. High protein binding of diazepam results in greater free drug in elderly in contrast to lesser change in dose requirements of midazolam. The latter may cause severe hypotension in the elderly (Committee on Safety of Medicines warning).

Table 6.1 Half-life of benzodiazepines

Propofol. 50% reduced dose requirement. More enhanced CVS depression and greater hypotensive effect (diastolic > systolic). Reduce hypotension on induction by slower rate of injection. Propofol reduces postoperative mental confusion compared with other induction agents.

Volatiles. MAC decreases linearly with age. Volatiles with rapid elimination, e.g. desflurane, may reduce postoperative mental confusion. Isoflurane, desflurane and sevoflurane have fewer cardiovascular side-effects than other volatiles.

Opioids (Table 6.2). Smaller V_D with higher initial plasma concentrations. Increased elimination half-life (↓ clearance greater than ↓ V_D). Decreased protein binding of pethidine with increasing age.

Table 6.2 Half-life of opioids

Muscle relaxants. Reduced plasma cholinesterase but minimal effect on hydrolysis. There are conflicting results for atracurium and vecuronium. Probably little change in initial dose requirements but prolonged elimination. No change in dose requirements or elimination of cisatracurium, but 30% increase in time to effective block. Pancuronium and gallamine cause tachycardia, worsening any myocardial ischaemia.

Anticholinergics. No change in dose but slower onset of action and prolonged muscarinic side-effects.

Local anaesthetics. Decreased elimination of lidocaine and bupivacaine with increased risk of toxicity.

Regional anaesthesia

In the elderly, regional anaesthesia decreases postoperative mental confusion and allows immediate recognition of angina, TIAs and mental confusion during TURP. Although some studies show benefits from regional anaesthesia, e.g. reduced incidence of MI, DVT, confusion, postoperative hypoxia, and decreased blood loss, others have reported increased risk of CVA and intraoperative hypotension. Meta-analysis shows trend towards reduced early mortality using regional anaesthesia.

Central anticholinergic syndrome

General principles of anaesthetic management

History

Epidemiology

The average number of reported suspected anaphylactic reactions related to anaesthesia is 55 p.a. compared with an average of 319 for all drugs. A total of 10% of anaesthetic reports were of fatalities, compared with 3.7% for all drugs reported. It is estimated, however, that there may be as many as 175–1000 severe reactions in the UK each year (1:5000–25 000 anaesthetics), with an overall mortality of 3.4%.

Some 90% occur within 10 min of drug administration. It is more common in females (5:1 neuromuscular blocking drugs; 3:1 thiopentone).

Types of allergic reaction

Hypersensitivity reactions

Mast cells

Found in perivascular tissue, gut mucosa, lung and skin. Up to 10% of their total weight is histamine. Stimulation causes release of histamine, eosinophil and neutrophil chemotactic factors, leukotrienes, prostaglandins, platelet-activating factor and kinins.

Hypersensitivity to drugs (Fig. 6.1)

In a French study (Laxenaire 2001), overall incidence of reactions was 1 in 13 000 anaesthetics, while the incidence of anaphylaxis to neuromuscular blocking agents was 1 in 6500 anaesthetics. Causes included neuromuscular blocking drugs (62%), latex (17%), antibiotics (8%), hypnotics (5%), colloids (3%) and opioids (3%).

Figure 6.1 Causes of life-threatening allergic reactions during anaesthesia.

(Data from Laxenaire 2001.)

Cross-reactivity may occur between drugs with similar structures, causing a type I hypersensitivity reaction to a drug to which the patient has not previously been exposed. In 70% of patients found to be allergic to a neuromuscular blocking drug, cross-reactivity was found to others; 17% of those allergic to a neuromuscular blocking drug had not had anaesthesia before.

Clinical symptoms (Fig. 6.2)

Awake patients may experience a metallic taste and a sense of impending doom. Commonest symptoms are hypotension (80%), rash/erythema (50%) and bronchospasm (36%). Tachycardia due to chronotropic effects of histamine and secondary release of adrenaline and noradrenaline. SVR is decreased by as much as 80% due to direct effect of histamine. Other symptoms include:

Figure 6.2 The first clinical feature of an anaphylactic reaction.

(Data from Whittington and Fisher 1998.)

CVS. Arrhythmias, pulmonary hypertension

Respiratory. Pharyngeal and laryngeal oedema (24%), rhinitis, pulmonary oedema

GI. Nausea and vomiting, diarrhoea, abdominal colic

Other. Generalized oedema (7%).

Factors which increase severity included asthma, β-blockade and neuraxial anaesthesia. All of these states are associated with reduced endogenous catecholamine response.

Treatment

Prophylaxis

Prophylaxis with antihistamines (H₁ and H₂) does not reduce the incidence of allergic reactions, but reduces mortality if they occur.

Screening

There is no method of predicting sensitivity to anaesthetic drugs. A history of previous exposure is not necessary for an anaphylactic reaction. The use of test doses of intravenous drugs is not an appropriate method of testing for anaphylaxis. Anaphylaxis has resulted from very small doses.

Anaesthesia for the atopic patient

There is some evidence that mast cells may degranulate more readily in atopic patients, but no evidence that atopic patients are any more susceptible to drug-mediated allergic reactions. Consider using drugs with low incidence of reaction, i.e. ketamine, etomidate and pancuronium.

Blood donors

Some 17 million units of blood are donated in Europe each year. Each unit is screened for antibodies to:

Blood groups

The ABO blood groups are summarized in Table 6.3.

Table 6.3 Summary of ABO blood groups

Coagulation cascade

Products

Whole blood

• 500 mL per bag with a haematocrit of 0.40

• No functioning platelets after 2–3 days; ↓ 2,3-DPG by 2 weeks

• Normal concentrations of albumin and clotting factors, except factors V and VIII, which are reduced to 10–20% of normal

• Not sterilized, so there is a risk of transmitted pathogens.

Red cell concentrate (packed cells): 2.2 × 10⁶ units used p.a. in the UK

• 250 mL per bag with haematocrit of 0.60

• No functioning platelets; 2,3-DPG levels maintained for 14 days

• Storage is 35 days with SAGM (saline, adenine, glucose, mannitol); 42 days with A-CPD (adenine, citrate, phosphate, dextrose).

Platelet concentrates: 260 000 units used p.a. in the UK

• Usually as a pool of 5–6 single unit donations; 4 units of platelets contain 1 unit FFP

• High incidence of transfusion-related acute lung injury (TRALI) associated with platelet transfusions. Usually due to an interaction between leucocyte antibodies in donor plasma and the corresponding antigen in the patient

• Infection risk. Increased by multiple donors and platelets >3 days old

• Use ABO-compatible platelets. Maximum storage is 5 days at 4°C.

Fresh frozen plasma (FFP): 300 000 units used p.a. in the UK

• Prepared from plasma from single donation; 150 mL per bag

• Contains all clotting factors, albumin and gammaglobulin

• Use within 24 h of thawing if kept at 4°C

• Must be ABO-compatible and Rh(D)-negative if recipient is a Rh(D) fertile female

• Risk of anaphylactic reactions.

Cryoprecipitate: 100 000 units used p.a. in the UK

• Precipitates from FFP when slowly thawed; supplied as 6–8 units

• High in factor VIII, fibrinogen and von Willebrand factor

• Indicated for DIC and von Willebrand’s disease.

Human albumin solution

Prepared by fractionation of multiple units of plasma giving 96% albumin and 4% globulin. Available as 4.5 or 20% (hyperoncotic) solution. Each 20 g of albumin requires 20 000 blood donations. Pasteurized at 60°C for 10 h to kill all microorganisms including viruses.

Factor VIII concentrate

• Freeze-dried protein as 250 units

• Sterilized to inactivate viruses.

Factor IX concentrate

• Freeze-dried protein as 250 units

• Sterilized to inactivate viruses

• Also contains factors II and X.

Immunoglobulin products

• Fractionation of plasma to produce pool with >90% IgG

• No risk of viral transmission

• Used for immune thrombocytopenia and immunodeficiency states.

Recombinant blood products

Recombinant FVIIa

rFVIIa initially developed to treat bleeding in haemophiliacs. FVIIa binds to tissue factor on damaged vascular beds to activate FIX and FX. The subsequent conversion of prothrombin to thrombin, activates platelets FVIII, FV and FXI and results in a large thrombin burst to transform fibrinogen to fibrin (Fig. 6.3). A recent meta-analysis of seven randomized clinical trials showed a reduction in blood transfusion requirements with no major safety concern (Ranucci 2008). Concerns remain regarding possible risks of thrombotic events.

Figure 6.3 Clotting cascade.

Transfusion reactions

Acute

• Haemolysis – due to antibodies directed against red cells

• Fever – donor leucocytes attack host red cells

• Anaphylaxis – due to antibodies directed against recipient IgA

• Transfusion-related acute lung injury – due to donor antibodies directed against leucocytes. Clinically identical to ARDS

• Hyperkalaemia – 5–10 mmol K⁺ in a unit of blood stored for 4–5 weeks. Effects of additional K⁺ are exacerbated by acidosis and hypothermia. Hyperkalaemia is usually transient

• Citrate toxicity – citrate is added as a preservative to bind excess calcium and prevent clotting. Metabolized to bicarbonate. Excess causes metabolic alkalosis

• Acid–base disturbance – citrate from preservative and lactate from red cells

• Hypocalcaemia – citrate anticoagulant binds ionized calcium; ↓ BP, ↓ pulse pressure. Give CaCl₂ only if there are symptoms/signs (not Ca²⁺ gluconate, which must be metabolized to release free Ca²⁺)

• Febrile reaction – due to bacterial contamination

• Microemboli – aggregates of all cellular components, increase with age of blood. Cause complement activation, haemolysis and thrombocytopenia. Removed by 170 μm filter; +/– 40 μm screen and depth filters

• Hypothermia – left shift of O₂ dissociation curve, platelet and clotting dysfunction

• Air embolus

• Fluid overload.

Delayed

• Haemolytic transfusion reaction – from red cell antibodies

• Graft-versus-host disease

• Alloimmunization (reaction to minor foreign antigens) – 10% of all transfusion reactions:

– red cell antibodies including anti-Rh(D)

– leucocyte antibodies

– platelet antibodies

• Viral infection – hepatitis B (<1:20 000 units) and C (<1:1 000 000 units), HIV (<1:4 000 000 units), cytomegalovirus, parvovirus (causes aplastic anaemia in sickle cell patients)

• Other infections – syphilis, malaria, trypanosomiasis

• Prions – risk of acquiring variant Creutzfeldt–Jakob disease (vCJD) is unknown. To minimize risk, UK National Blood Service leuco depletes blood, obtains plasma for fractionation from countries other than the UK and excludes donors who themselves received transfusions before 1980. At present, no test for vCJD exists.

• Tumour recurrence – increased risk

• Sensitization – resulting in antibody formation and subsequent difficulties with cross-matching

• Iron overload – occurs with repeated transfusions.

Massive blood transfusion

Defined as the acute administration of more than 1.5 times the patient’s blood volume, or replacement of the patient’s total blood volume within 24 h.

Blood groups for urgent transfusion are:

• Rh(D)-negative if patient not cross-matched

• Uncross-matched blood (type-specific) if patient’s blood group is known

Blood transfusions can be avoided by:

• reducing blood loss – hypotensive anaesthesia, antifibrinolytic agents

• tolerating a lower haematocrit

Guidelines for Autologous Blood Transfusion

British Committee for Standards in Haematology Blood Transfusion Task Force 1997

Summary

The purpose of all forms of autologous transfusion (acute preoperative haemodilution and preoperative donation or intraoperative cell salvage) is to avoid the transfusion of allogeneic blood and the associated risks. Autologous transfusion procedures are not usually acceptable to Jehovah’s Witnesses, although some accept intraoperative cell salvage.

Intraoperative cell salvage

Indications. Elective and emergency surgery with expected blood loss >20% total body volume.

Contraindications. Bacterial contamination of wound, malignant disease and sickle cell disease.

Acute preoperative haemodilution and preoperative donation

Indications. Elective surgery with expected blood loss >20% total body volume.

Contraindications. Aortic stenosis, unstable angina, and moderate to severe left ventricular impairment (Napier et al, 1997).

Blood Transfusion and the Anaesthetist – Red Cell Transfusion

Association of Anaesthetists of Great Britain and Ireland, June 2008

Summary

1. The decision to transfuse should always be made on an individual patient basis.

2. Patients need not be transfused to achieve a ‘normal’ haemoglobin concentration.

3. Anaesthetists should play a lead role in good preoperative assessment and preparation.

4. Departmental guidelines should be drawn up on matters of blood transfusion and be readily available for reference.

5. A permanent record of the administration of each unit of red blood cells is required by European law.

6. Record the reason for preoperative and postoperative transfusions in the clinical notes.

7. Local surgical blood ordering schedules, once developed, need to be reviewed at regular intervals by auditing red cell use.

8. Every Hospital Transfusion Committee is advised to include a representative from the Department of Anaesthesia.

Blood Transfusion and the Anaesthetist – Blood Component Therapy

Association of Anaesthetists of Great Britain and Ireland, December 2005

Recommendations

• Assessment of haemostasis in the preoperative period can reduce perioperative blood loss.

• Red cell concentrates do not contain coagulation factors or platelets, so the use of blood components (fresh frozen plasma (FFP) and platelets) needs to be considered early in managing a patient with massive haemorrhage.

• Emergency use of blood components requires assessment of haemostasis in advance of administration even if empirical use is necessary.

• The use of near-patient testing devices can improve decision making on the use of blood components.

• Thawed FFP can be stored at 4°C and can be used safely within 24 h.

• Thawed FFP kept at room temperature must be infused within 4 h.

• Vitamin K ± prothrombin complex concentrate (PCC) is recommended to reverse warfarin. FFP is indicated when there is severe bleeding or when PCC is unavailable.

• Platelet transfusion in the bleeding patient, or a patient requiring urgent surgery, is indicated at a platelet count <50 × 10⁹.L^-1 but in stable non-bleeding patients in intensive care, a trigger of 10 × 10⁹.L^-1 is acceptable.

• Component therapy should not be used to make regional anaesthesia possible if there are alternative anaesthetic methods available.

Blood Transfusion and the Anaesthetist – Intraoperative Cell Salvage

Association of Anaesthetists of Great Britain and Ireland, September 2009

Recommendations

• The use of intraoperative cell salvage (ICS) reduces the demand on allogeneic (donor) red cells and is a cost-effective measure.

• Trusts should provide the resources required to set up and maintain an ICS service in a safe and appropriate manner.

• Each Trust needs to ensure there is a clinical lead for ICS.

• A member of the theatre management team is responsible for ensuring overall management and facilitation of the ICS service.

• All personnel using ICS must be adequately trained and competent in its use.

• Preoperative assessment clinics should provide information on ICS to patients.

• All ICS cases undertaken require documentation and audit of use to enable future service planning and quality assurance.

Operative indications

• Anticipated blood loss >1000 mL or >20% estimated blood volume.

• Patients with a low HB or increased risk factors for bleeding.

• Patients with multiple antibodies or rare blood types.

• Patients with objections to receiving allogeneic (donor) blood.

Substances that should not be aspirated in the ICS system

• Antibiotics not licensed for i.v. use

• Iodine

• Topical clotting agents

• Orthopaedic cement.

Special circumstances

Malignancy – Concerns regarding reinfusion of malignant cells. Recent studies of the use if ICS during surgery for hepatocellular and bladder/prostate cancer have shown no difference in recurrence rates or long-term survival in patients receiving ICS; conversely, there is good evidence that allogeneic blood transfusion is an independent factor for postoperative infection and disease recurrence. The use of ICS in urological malignancies was approved by NICE in 2008.

Obstetrics – No proven cases of amniotic fluid embolus caused by reinfusion of salvaged blood. The use of ICS in obstetrics was approved by NICE in 2005.

Bowel contamination – Concern regarding infection risk if contaminated blood (with microorganisms) is reinfused. A RCT of ICS in abdominal trauma showed no increased infection risk when using ICS. Some case reports have suggested that reinfused blood in these patients may cause hypotension.

• transfusing autologous blood – prior donation, use of cell saver

• artificial blood

• erythropoietin.

Antifibrinolytic agents

Antifibrinolytic agents, e.g. tranexamic acid (aprotinin was withdrawn because of concerns about excess mortality and renal failure), bind to plasminogen and plasmin to interfere with their ability to split fibrinogen. Prostatic plasminogen activator is released during prostate surgery to cause bleeding, inactivated by antifibrinolytic agents. Antifibrinolytic agents may reduce bleeding in cardiac surgery following cardiopulmonary bypass.

Artificial blood (Fig. 6.4)

Perfluorocarbons. Inert carbon chains with oxygen solubility 20 times that of plasma. One study showing that perfluorocarbon emulsion may limit transfusion requirements, but trend towards greater morbidity and mortality (Spahn et al 2005).

Figure 6.4 Oxygen dissociation curve for oxygen-carrying molecules.

Recombinant Hb (rHb1.1). Modified human haemoglobin tetramer cross-linked with a glycine bridge between the alpha subunits. Produced from E. coli or yeast. Cross-linking prevents renal excretion. Cleared by the reticuloendothelial system within 24 h.

Purified Hb. From expired red cells, e.g. diaspirin cross-linked haemoglobin. Now abandoned because of higher mortality in some trauma studies.

Jehovah’s Witnesses

For the life of the flesh is in the blood: and I have given it to you upon the altar to make atonement for your souls: for it is the blood that maketh an atonement for the soul. Therefore I said unto the children of Israel, No soul of you shall eat blood, neither shall any stranger that sojourneth among you eat blood.

(Leviticus 17: 10–12; see also Genesis 9: 3–4 and Acts 15: 28–29).

There are an estimated 145 000 Jehovah’s Witnesses in the UK. They refuse administration of all blood and usually all blood products. They will allow blood to be retransfused if it has not lost contact with the circulation, e.g. cardiopulmonary bypass. The Children and Young Persons Act 1933 states that parents have a duty of care to their children which is not fulfilled if permission for a life-saving blood transfusion is withheld. Doctors can apply to the courts for permission to give blood against the parents’ wishes, but in an emergency, blood can be given to children without consulting the courts. Children under the age of 16 can consent to a blood transfusion if they understand the issues involved, but may not refuse blood.

Clinical issues

Anaesthetists have the right to refuse to anaesthetize an elective case (when referral can be made to other colleagues) but must anaesthetize an emergency case if failure to do so would harm the patient. Ideally, consultant staff should be involved with patient care.

Preoperative assessment should take place as early as possible. Anaemia should be treated. Use of iron supplements and erythropoietin should be considered. Patients must be seen alone to avoid undue influence from other family/church members. The patient must be made fully aware of the risks of refusal of blood products. It must be clarified which blood products and techniques (e.g. cell saver) are acceptable.

Intraoperative management

Blood loss >500 mL in adults is associated with increased mortality. Techniques to minimize blood loss include positioning to avoid venous congestion, hypotensive anaesthesia, use of tourniquets, meticulous haemostasis, use of vasoconstrictors, acute hypervolaemic haemodilution and use of a cell saver. Antifibrinolytics (e.g. tranexamic acid) may also reduce blood loss. Recombinant factor VIIa has been used successfully in these patients.

Postoperative care

• Early detection and correction of postoperative oozing

• Consider elective ventilation to increase oxygen delivery

• Active cooling reduces oxygen demand and increases dissolved oxygen carriage

• Hyperbaric oxygen therapy may also be of benefit.

Management of Anaesthesia for Jehovah’s Witnesses

Association of Anaesthetists of Great Britain and Ireland 2005 (2E)

Recommendations

1. Wherever possible, consultant staff (anaesthetists and surgeons) should be directly involved throughout the care of Jehovah’s Witness patients.

2. Departments of anaesthesia should review their procedure for being alerted at an early stage of the scheduling of Jehovah’s Witness patients for elective surgery.

3. Departments should keep a regularly updated list of those senior members prepared to care for followers of the Jehovah’s Witness faith.

4. In an emergency, an anaesthetist is obliged to care for a patient in accordance with the patient’s wishes.

5. Properly executed Advance Directives must be respected and special Jehovah’s Witness consent forms should be widely available for use as required.

6. All Jehovah’s Witnesses must be consulted individually, whenever possible, to ascertain what treatments they will accept.

7. Discussions with individual Jehovah’s Witness patients should be fully documented and their acceptance or rejection of treatments recorded and witnessed.

8. In the case of children, local procedures for application to the High Court for a ‘Specific Issue Order’ should be reviewed and available for reference.

9. A ‘Specific Issue Order’ or equivalent should only be applied for when it is felt to be entirely necessary to save the child in an elective or semi-elective situation.

10. In a life-threatening emergency in a child unable to give competent consent, all life-saving treatment should be given, irrespective of the parents’ wishes.

Consumptive coagulopathies

Disseminated intravascular coagulation (DIC)

Consumptive coagulopathy associated with activation of both coagulation and fibrinolytic pathways. Commonest causes are sepsis, obstetric-related conditions or shock. Treatment should be guided by clinical signs and coagulation results, to include platelet concentrate, fresh frozen plasma, cryoprecipitate (a source of fibrinogen) and red cells. Antifibrinolytic agents may risk permanent clot formation. Use of heparin is controversial, but may be of benefit in amniotic fluid embolism.

Thromboelastography

Thromboelastography (TEG) was first described in 1948, but the risks of blood product transfusion and financial costs have led to a renewed interest in improving coagulation management.

Principles of TEG

TEG uses the viscoelastic changes of blood that are associated with fibrin polymerization. Clot formation is induced by putting whole blood in a low shear environment (which mimics sluggish venous flow). The patterns of shear-elasticity alteration reveal the kinetics of clot formation and growth, and the strength and stability of the formed clot. The kinetics of clot formation reflects the adequacy of quantitative factors available, while the clot strength/stability reveals the ability of the clot to perform the work of haemostasis.

The thrombelastograph consists of a larger vertical cylinder within which sits a smaller cylinder. The outer cylinder (cuvette) of the thrombelastograph oscillates at a fixed frequency. The internal cylinder (pin) of the thrombelastograph is free to move. As the blood sample placed between the cylinders clots, it forms a mechanical bond between the inner and outer cylinders of the thrombelastograph such that the oscillatory motion of the outer cylinder is transmitted to the inner cylinder. The stronger the clot, the greater the adhesion between the two cylinders and the larger the transmitted oscillation of the inner cylinder. The oscillations of the smaller cylinder are amplified to create a TEG trace.

TEG endpoints (Fig. 6.5)

R time

The time from the start of measurement until the start of clot formation. Reflects the initiation of clotting, thrombin formation, and the start of fibrin polymerization.

Figure 6.5 A thromboelastograph tracing, showing the endpoints used for TEG analysis.

Prolonged R time is caused by:

• Factor deficiency

• Heparin

• Severe thrombocytopenia

• Severe hypofibrinogenaemia.

Short R time is caused by:

• Hypercoagulable states.

K time

The time from starting clot formation until amplitude of 20 mm is reached. Represents fibrin polymerization, stabilization of the clot with platelets and FXIII.

Prolonged by:

• Factor deficiency

• Thrombocytopaenia

• Thrombocytopathy

• Hypofibrinogenaemia.

Shortened by:

• Hypercoagulable state.

Angle (α)

Measures the rapidity of fibrin build-up and cross-linking (clot strengthening).

Increased angle is caused by:

• Hypercoagulable state.

Decreased α is caused by:

• Hypofibrinogenaemia

• Thrombocytopaenia.

Maximum amplitude (MA)

A direct function of fibrin and platelet bonding via GPIIb/IIIa, reflecting ultimate clot strength. Correlates with platelet numbers and function, and fibrinogen levels.

Increased by:

• Hypercoagulable state.

Decreased by:

• Thrombocytopaenia

• Thrombocytopathy

• Hypofibrinogenaemia.

LY30 or LY60

Measures percentage decrease in amplitude at 30 or 60 min post-MA, indicating the degree of fibrinolysis. (Normal range <7.5%.)

This TEG trace is charted over time, producing a distinct shape according to the coagulation profile (Fig. 6.6).

Figure 6.6 Common patterns of abnormal TEG profiles.

Advantages of TEG

• Provides initial results within 10–20 min

• Good at differentiating between surgical and coagulopathic bleeding (negative predictive value >90%)

• Has been shown to reduce transfusion requirements.

Limitations of TEG

• Poor at detecting platelet dysfunction (TEG uses celite or kaolin activation of the clotting cascade. This results in supra-physiological thrombin generation, which is sufficient to activate even platelets inhibited by aspirin or clopidogrel)

• Whole blood TEGs are performed at 37°C, masking any anticoagulant effects of hypothermia.

Epidemiology

There are 10 000 burns admissions p.a. in the UK, of which 600 are fatal; 35% of burn injuries occur in children. Most burns are scalds (children), flame burns and flash burns (adults); also electrical and chemical burns. Cold injury (frostbite) is rare in the UK.

Treatment of burn injury

Airway

Direct thermal injury, toxic gases and smoke inhalation cause:

• upper airway oedema and obstruction

• lung parenchymal damage

• carbon monoxide poisoning

• cyanide poisoning (burning plastic).

Breathing

Monitor respiratory function, especially if there is inhalational injury. Indicators of an upper airway burn include voice changes, CXR changes, carboxyhaemoglobinaemia >15%, or compromised arterial blood gases.

Humidify inspired gases if there is upper airway burn. Intubate immediately if severe airway burn, since facial oedema will develop rapidly over the initial 24 h following a facial burn and may make intubation very difficult.

Carbon monoxide poisoning. 1000 deaths p.a. in the UK. The symptoms of CO poisoning are given in Table 6.4. HbCO results in over reading of the pulse oximeter. The half-life of carbon monoxide (250 times the affinity of O₂ for Hb) is:

• room air – 5 h

• 100% O₂1 h.

Table 6.4 Symptoms of carbon monoxide poisoning

%HbCO	Symptoms
0–10	None
10–20	Headache, malaise
30–40	Nausea and vomiting, slowing of mental activity
>60–70	CVS collapse, death. Consider hyperbaric O2 therapy

Hyperbaric oxygen treatment is recommended with COHb >20%, loss of consciousness at any stage, neurological signs/symptoms arrhythmias, or pregnancy. Reduces the risk of serious neurological deficit and shortens recovery.

Cyanide poisoning. Causes metabolic acidosis, raised lactate, arterial hypoxaemia and increased anion gap. Consider treatment with cyanide-chelating agents (dicobalt edetate) or agents accelerating cyanide metabolism (sodium thiosulphate).

Circulation

Risk of profound hypovolaemia with hypotension. Early fluid shifts result in loss of fluid from the plasma into the extracellular tissue around the burn. This fluid is similar in composition to plasma with equal electrolyte content but with slightly less protein. If crystalloid is used for resuscitation, larger volumes are necessary and may result in tissue oedema. Fluid loss is maximal in the first few hours and returns to basal levels by 36 h.

Blood loss during surgical debridement may be rapid and exceed 2 mL/kg per 1% of burn desloughed.

Extent and depth of burn

Burn size. This is estimated using the ‘Rule of Nines’ (Fig. 6.7).

Figure 6.7 ‘Rule of Nines’ for assessing burn area.

Depth of burn

Superficial. Damage to epidermis. Erythema but no blistering. Painful. Heals in 2–3 days.

Partial thickness. Destruction of epidermis and dermis with formation of blisters. If deep, may also include islets of fat. Painful. Heals within 10 days as fresh epidermis grows out from hair follicles but deep partial thickness burns may be slow to heal.

Full thickness. Complete loss of epidermis and dermis down to subcutaneous fat. Loss of pain receptors renders burn painless. The burn is either white or charred with eschar. Heals by wound contraction and thus if circumferential may require escharotomies in the acute stage.

Fluid replacement. Formal fluid resuscitation is commenced in adults with >15% burns or in children with >10% burns. Ringer’s lactate is the crystalloid of choice. Hypertonic saline may reduce fluid volumes and oedema, but some studies have shown that it causes hypernatraemia, renal failure and increased mortality.

These regimens are given in addition to the normal daily fluid requirements (usually given as 5% dextrose or dextrose saline). Volumes may need increasing if clinical indicators show inadequate resuscitation (mental status, vital signs, urine output, capillary refill, CVP, etc.).

Check electrolytes, haematocrit and plasma and urine osmolality every 4 h. Low volume urine with osmolality >450 suggests continuing hypovolaemia. Transfuse blood if haematocrit <0.3.

Common fluid replacement formulae:

• Parkland (commonest in UK)

– 4 mL/kg crystalloid × % burn

– (½ given over first 8 h, ¼ over next 8 h, ¼ over next 8 h).

• Muir and Barclay (Mount Vernon formula)

– 0.5 mL/kg colloid (PPF/albumin) × % burn given over 4, 4, 4, 6 and 6 h.

• Brook

– 0.5 mL/kg colloid and 1.5 mL/kg crystalloid × % burn

– (½ given over first 8 h, ¼ over next 8 h, ¼ over next 8 h).

Infection

May worsen depth of burn, risks spreading to become a systemic infection and may destroy any skin grafts. Patients at high risk both from loss of protective skin barrier and from generalized immunosuppression.

Nurse in as clean an area as possible because of high risk of infection. Take measures to avoid cross-infection. Use topical antimicrobial prophylaxis with silver sulphadiazine cream (Flamazine).

Antibiotic cover is necessary to cover dressing changes. Systemic antibiotics should not be given routinely.

Hypothermia

Impaired homeostatic control and heat loss through burns result in rapid onset of hypothermia, accelerated by general anaesthesia and cold fluids. Keep room at 30°C to minimize energy requirements and ensure use of blood warmer and heated mattress.

Multiple anaesthetics

Are required for dressing changes and skin grafting. Monitoring (e.g. ECG dot placement) may be difficult with extensive burns. Venous access may have to be gained through burnt tissue or by a cutdown.

Nutrition and GI

Early feeding is vital because of high catabolic state. NG tube may be necessary for feeding and to prevent acute gastric dilatation. Gastric stasis is common, in which case a nasojejunal tube is necessary. Calculate amount of feed needed according to Sutherland or modified Curreri formula. Aim for a calorie:nitrogen ratio of 100:1. Give gastric stress ulcer prophylaxis. Monitor blood sugar closely.

Analgesia

Any burns less than full thickness require large doses of opioid analgesia.

Surgical management

Superficial burns usually heal spontaneously within 10 days and do not require surgery.

Partial-thickness burns require frequent debridement and may require grafting if unhealed by 3 weeks.

Full-thickness burns require early debridement and grafting. Although early debridement of a large area further traumatizes the patient and may result in loss of a large blood volume, a delay in debridement risks wound colonization and septic shock and prolongs the catabolic state following injury. If full-thickness burns are not grafted, they may never heal, or if they do they will result in contractures.

Advantages